tbuckley/cabot-search huggingface dataset:
3D Augmented reality-guided robotic-assisted kidney transplantation: Revealing the concealed
Authors: A. Piana, A. Gallioli, P. Diana, A. Territo, J.M. Gaya, P. Gavrilov, Ó. Rodriguez Faba, J. Huguet, L. Guirado, C. Facundo, R. Campi, A. Bellin, D. Amparore, S. Serni, J. Palou, F. Porpiglia, A. Breda
Journal: European Urology (2022)
Alleviating the click fatigue on clinicians to improve referrals for colorectal cancer screening.
Authors: Robby Amin, Lorriane Achieng Odhiambo, Sayeda Ali, KM Islam, Joycelyn W Yates, James Hotz, Koosh Desai, Cynthia George, Katreena Mitchell, Lynn M. Durham, Sheryl G. A. Gabram, Jorge Cortes
Journal: Journal of Clinical Oncology (2022)

11021 Background: The impact of clinician burnout on patient care is pervasive across medical delivery systems. The effects are also felt in preventive care where cancer screening efforts rely on clinician referrals through the electronic medical records (EMRs). Though designed to support healthcare, EMRs are a significant source of clinician burnout given the number of clicks or navigation time needed to refer a patient. This is a barrier to Patient Navigation (PN) when ordered tests do not materialize into screenings or when clinicians order labs/imaging and the pending orders are not created. This causes frustration for all clinical staff involved, delays the workflow processes, and leads to missed opportunities for PN. We implemented an ‘order set’ intervention to reduce the click burden linked to colorectal cancer (CRC) screening referral among clinicians in South Georgia. Methods: The ‘order set’ intervention was developed to facilitate PN for a Colorectal Cancer Control Program (CRCCP) aimed at implementing Evidence-Based Interventions to increase CRC screening rates in Georgia. The ‘order set’ was designed to address workflow issues by consolidating steps associated with CRC screening. This reduced typing input and the need to click between multiple windows within the EMR while making a referral to PN. The intervention was piloted in the Albany Area Primary Health Care (AAPHC) system after modifications were made to the EMR and clinician workflows. The monthly CRC screening rates continue to be generated and tracked post-implementation. Results: The use of the ‘order set’ reduced the click burden from 78 to 7 inputs and clinician EMR interaction time from 110 seconds to 29 seconds. Providers from 4/7 clinics have adopted the ‘order sets’ when making referrals for CRC screening. Two clinics provided post-implementation screening data. The pre-implementation screening rates for one clinic were comparable (August = 59.3%, September = 57.6%) to post-implementation (October = 56.3%, November = 56.6%, December = 57.2%), while the second clinic showed some increase (August = 58.6%, September = 60%) vs. (October = 61%, November = 62.1%, December = 62.8%). Conclusions: The ‘order sets’ intervention reduced the time clinicians spent creating referrals for CRC screening, including fecal immunochemical tests (FIT) and colonoscopies. Additional follow-up and rollout to clinics participating in the program is underway to evaluate further the impact of the order sets on CRC screening outcome and process measures, including qualitative interviews with clinicians. There is significant potential in the application of order sets to various workflow processes to aid in preventative health efforts. Challenges linked to the COVID-19 pandemic and staff turnover affected acquisition of patient referral data.
Cardioprotection by limb remote ischemic preconditioning in rats: discrepancy between meta-analysis and a three-center in vivo study
Authors: N Sayour, GB Brenner, A Makkos, CS Kovacshazi, TG Gergely, H Tian, V Zenkl, P Bencsik, A Heinen, R Schulz, GF Baxter, CJ Zuurbier, Z Voko, P Ferdinandy, Z Giricz
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart Program funded by the National Research, Development and Innovation Office of Hungary Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the Therapeutic development thematic programme of the Semmelweis University Purpose and aims Despite promising preclinical results on cardioprotection by remote ischemic preconditioning (RIPC), large-scale clinical trials show no reduction in infarct size (IS). This translational gap might be due to unknown confounding factors and lack of sufficient high-quality in vivo preclinical proof-of-concept studies. Therefore, here we performed randomized, blinded in vivo studies in three study centers using the most often reported methodological settings, as well as a systematic review and meta-analysis of RIPC studies. Methods and Results Male Wistar rats were subjected to 20 to 45 min cardiac ischemia followed by 120 min reperfusion with or without preceding RIPC by 3 or 4×5-5 min occlusion/reperfusion of one or two femoral vessels by clamping, tourniquet, or pressure cuff. RIPC did not reduce IS, microvascular obstruction, or arrhythmias at any study centers. Systematic review and meta-analysis focusing on in vivo rat models of myocardial ischemia/reperfusion injury with limb RIPC showed that RIPC reduces IS by 21% on average; however, a tendency for publication bias towards positive results was found. In addition, our systematic review showed methodological heterogeneity and insufficient reporting quality in a high proportion of studies. Conclusion We report for the first time the lack of cardioprotection by RIPC in rats, assessed in individually randomized, blinded in vivo studies, involving multiple study centers. Although unanimously showing cardioprotection by RIPC, the majority of reviewed studies were inadequately reported, and under-publication of neutral studies is plausible. Methodological confounding factors leading to the discrepancy between meta-analysis and the present studies cannot be identified; insufficient reporting quality, heterogeneity of the applied settings, and selection bias against studies with neutral outcome may contribute to this discrepancy. More preclinical studies with adequate quality control, together with publication of neutral studies, are required to support development of clinically translatable cardioprotective interventions.
Diagnostic accuracy, concordance and certainty with 68Ga-PSMA-11 PET/MRI fusion compared to mpMRI and 68Ga-PSMA-11 PET/CT alone for prostate cancer diagnosis: A PRIMARY trial sub-study
Authors: P.N. Doan, W. Counter, G. Sheehan-Dare, N. Papa, B. Ho, J. Lee, V. Liu, J. Thompson, S. Agrawal, M. Roberts, O. Algharzo, J. Buteau, M. Hofman, D. Moon, D. Murphy, P. Stricker, L. Emmett
Journal: European Urology (2022)
Patterns and prevalence of pathogenic germline mutations using multi-gene panel testing in patients with ovarian cancer: The Jordanian Exploratory Cancer Genetics (Jo-ECAG) Ovarian Study.
Authors: Khansa Al-Azzam, Hala Abu-Fares, Areej Abu Sheikha, Lama Abujamous, Mais Alkyam, Hira Bani Hani, Rayan Bater, Brandie Heald, Edward D. Esplin, Hikmat Abdel-Razeq
Journal: Journal of Clinical Oncology (2022)

e17593 Background: Ovarian cancer is one of the most common gynecological malignancies. Because of the absence of effective screening methods, ovarian cancer is usually diagnosed at late stages contributing to high mortality rates. Patients with BRCA1 and BRCA2 pathogenic germline variants (PGVs) harbor elevated risk of developing both ovarian and breast cancer. Identifying PGVs may help optimize management options and improve outcomes. The worldwide prevalence of gene mutations is variable. Multiple series have demonstrated differences in PGVs according to ethnicity and geographic area. Data about prevalence of the aforementioned PGVs among Arab patients with ovarian cancer is not well understood. Methods: Patients with epithelial ovarian, fallopian tube or primary peritoneal carcinomatosis were referred for 20 or 84-multi-gene panel testing (MGPT). All patients had their diagnosis, treatment and follow up at a single cancer center. Following detailed counselling, MGPT was performed at no-cost to all patients at two reference laboratories. Descriptive statistics were performed, groups outcome was determined by two-tailed Fisher’s exact test and unpaired t-test. The study was approved by the Institutional Review Board (IRB) at King Hussein Cancer Center and all patients signed informed consent. Results: During the study period, 152 patients, median age (range): 50 (18-79) years were tested. Two patients had fallopian tube cancer, while all others had epithelial ovarian cancer. The majority (n = 100, 65.8%) had high-grade serous carcinoma, and 106 patients (69.7%) had metastatic disease on presentation. In total, 38 (25.0%) had PGVs while 47 (30.9%) others had variants of uncertain significance (VUS). PGVs were mostly in BRCA1 (n = 21, 13.8%) and in BRCA2 (n = 12, 7.9%), while only 5 (3.3%) had PGVs in non- BRCA1/2 genes ( CHECK2, MUTYH, PMS2, RAD51D, and RB1) . Age (&lt; 50 versus ≥50) at diagnosis, histological tumor subtype, and disease stage had no impact on pathogenic variant rates. However, PGVt rates were significantly higher (60.0%, p = 0.022) among patients with positive family history of ovarian cancer and 40.4% (p = 0.017) among patients with positive family history of breast cancer. The two patients with fallopian tube cancer were both positive for BRCA1 PGVs. Only one patient underwent prophylactic bilateral mastectomies. Conclusions: PGVs in patients with ovarian cancer are common among Arabs and mostly in BRCA1/2 and rates are significantly higher among patients with family history of ovarian or breast cancers.
Back to the future: Is the use of fasciocutaneous penile flap increasing in contemporary years for reconstructing the anterior urethra?
Authors: M. Bandini, C. Yepes, P. Joshi, S. Bhadranavar, S. Bafna, F. Montorsi, A. Briganti, A. Salonia, G. Barbagli, S. Kulkarni
Journal: European Urology (2022)
Development of combination strategies for focal adhesion kinase inhibition in diffuse gastric cancer.
Authors: Ke Peng, Adam Joel Bass
Journal: Journal of Clinical Oncology (2022)

e16057 Background: Diffuse gastric cancer (DGC) is an aggressive and frequently lethal pathological subtype of gastric cancer (GC). Since DGC often lacks genomic aberrations that indicate clear candidate therapeutic targets, it has been challenging to develop target therapies for this GC subtype. Our previous study highlighted the contribution of focal adhesion kinase (FAK) in the tumorigenesis of DGC, and the potential for small molecule FAK inhibitors to have efficacy in DGC. Currently, FAK inhibitors are under active clinical evaluation in several tumor types. To date, FAK inhibitor monotherapy has been tolerated in the clinic, but has shown only modest clinical efficacy in cancer treatment, which inspired us to explore targets for the combination with FAK inhibitors in DGC. Methods: We constructed the engineered murine DGC model of Cdh1 -/- RHOA Y42C/+ organoids, with Cdh1 (E-Cadherin) loss and RHOA Y42C mutation, in our previous study. Using this DGC organoids model, we performed genome-scale libraries of open reading frames (ORF) screen to identify candidate mechanisms of resistance to FAK inhibitors (defactinib or PF-573228). For the top hits found in ORF screen, further validations were performed in Cdh1 -/- RHOA Y42C/+ organoids and human DGC cell lines of NUGC4 and SNU668 to check whether they could function as candidates for the combination with FAK inhibitors. Besides, we used Digiwest, a high-throughput protein analysis assay, to investigate pathway alterations of Cdh1 -/- RHOA Y42C/+ organoids treated with FAK inhibitors (defactinib or PF-573228). We then explored whether the activated pathways were the candidates for the drug combination. Zero Interaction Potency (ZIP) model was used to measure the synergistic effect between the drugs. The combination strategies were also tested in vivo. Results: We identified that cyclin-dependent kinase 6 (CDK6) promotes FAK inhibitors (defactinib and PF-573228) resistance according to ORF screen, and CDK4/6 inhibitor, Palbociclib, enhances the efficacy of defactinib for DGC models. Furthermore, we demonstrated that FAK inhibitors (defactinib and PF-573228) treatment in DGC models leads to compensatory activation of MAPK pathway in DGC, and the RAF/MEK dual inhibitor VS-6766 effectively enhances the antitumor efficacy of FAK inhibitors in vitro and in vivo. Conclusions: These data suggest that combinations of FAK inhibitors with MAPK inhibitors or CDK4/6 inhibitors are promising treatment strategies for DGC that warrant further testing in clinical trials.
Plenary Session—The Patient Journey: Cancer Survivor Care
Authors: Shannon M. Ansbaugh, Gary Deng, Rev. George F. Handzo, Karen L. Syrjala, Jessica R. Bauman
Journal: Journal of the National Comprehensive Cancer Network (2022)

Quality survivorship care is critical for individuals dealing with the physical, mental, and emotional impacts of cancer and its treatment. Patients may not grasp the full traumatic impact of a cancer diagnosis until years later, but the mental health impacts of cancer can be significant. At the NCCN 2022 Annual Conference, a diverse panel discussed the cancer journey through the eyes of survivorship care, with voices representing both the patient and provider perspectives. Featured during the discussion were updates to the NCCN Distress Thermometer Problem List (to represent current psycho‐oncology best practices more accurately), NCCN recommendations for mental health screening, and the benefit of integrative medicine both to relieve symptoms and improve overall wellness. Empowering patients to become active participants in their own treatment and strong survivors afterward was the overriding theme throughout the panel discussion.
Renal Pelvis Immunoglobulin G4–Related Disease Mimicking Malignant Tumor
Authors: Zeyu Zhang, Yanfang Liu, Lu Zhang, Chao Cheng, Changjing Zuo
Journal: Clinical Nuclear Medicine (2022)

A space-occupying lesion in the left renal pelvis was found in a 56-year-old man. The patient voluntarily participated in a clinical trial of 68 Ga-FAPI in solid tumors. PET/CT images revealed an intense 18 F-FDG and 68 Ga-FAPI uptake in this lesion. Malignant tumor was suspected. The patient subsequently underwent laparoscopic partial nephrectomy. The postoperative pathological examination established the diagnosis of immunoglobulin G4-related disease.
Diurnal variation in thrombotic and fibrinolytic status in healthy volunteers
Authors: Y Gue, V Memtsas, R Kanji, D Gorog
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): East and North Hertfordshire NHS Trust Background Previous studies assessing markers of fibrinolysis in healthy volunteers and patients with coronary artery disease (CAD) indicate circadian variation, primarily attributable to changes in plasminogen activator inhibitor-1 (PAI-1) concentrations, the main inhibitor of fibrinolysis, peaking between midnight and 06:00 hrs, with a nadir at 01:00 hrs. Whether the elevated PAI-1 translates into a global impairment of fibrinolysis, is not known. Purpose It was our aim to assess diurnal variation in global fibrinolytic activity in healthy subjects. Methods A single centre, prospective, observational study was conducted in healthy volunteers. Blood samples were obtained at two different time points on the same day, with a minimum inter-sample interval of 8 hours and a maximum of 12 hours. Venous blood was assessed to determine global thrombotic and fibrinolytic status in native whole blood status using the automated, point-of-care Global Thrombosis Test (GTT). This utilises non-anticoagulated blood to assess the time taken to form an occlusive thrombus under high shear (occlusion time) and the time taken for spontaneous restart of flow as a measure of endogenous fibrinolysis (lysis time). Results A total of 25 healthy volunteers (36% male), aged 34±12 y were included. All were non-smokers with a BMI of 25 (22.3 – 27.5) kg/m². The median interval between samples was 8:05 [hh:mm] (IQR 8:30 – 9:10). Occlusion time was similar in the morning and evening samples (median 451s [389 – 590] vs. 524s [428 – 597], p=0.207). Lysis time was also similar between morning and evening (median 1792s [1622 -2097] vs. 1726s [IQR 1517 – 1891], p=0.265). Conclusion Compared to the known circadian variation of thrombotic and fibrinolytic activity attributable to PAI-1, global thrombotic and fibrinolytic status do not appear to exhibit diurnal variation. Further studies are needed to assess how this correlates to t-PA and PAI-1 levels and the status in patients with cardiovascular disease.
MEDB-28. CDK9 is a druggable mediator sustaining Myc-driven circuitry in medulloblastoma
Authors: Krishna Madhavan, Faye Walker, Dong Wang, Lays Martin Sobral, Ilango Balakrishnan, Angela Pierce, Natalie Serkova, Nicholas Foreman, Sujatha Venkataraman, Rajeev Vibhakar, Nathan Dahl
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Though long recognized as a master regulator of cell proliferation across a wide range of cancers, Myc has proven elusive to direct therapeutic targeting. The CDK9-containing PTEFb, complexed with either BRD4 or SEC, facilitates Myc-driven transcriptional programs and is necessary for sustaining expression of Myc itself. Advances in development of clinical-grade CDK9 inhibitors creates an opportunity to examine this as a rational therapy for Myc-driven medulloblastoma. METHODS: We used both RNAi depletion and a panel of pharmacologic agents to characterize the mechanistic and functional consequences of CDK9 inhibition in Myc-driven medulloblastoma. We used a combination of clonogenic assays and live cell imaging to assess the cytotoxic effects of CDK9 activity loss. We then performed a combination of CUT&amp;RUN and RNA-seq to evaluate alterations to Myc binding and downstream Myc-driven transcriptional programs. Finally, we employed orthotopic xenograft models of medulloblastoma to assess CNS penetration, tolerability, and anti-tumor efficacy of lead CDK9i candidate compounds. RESULTS: Genetic or pharmacologic inhibition of CDK9 leads to a loss of Myc expression and downregulation of hallmark Myc-driven transcriptional programs. This corresponds to a loss of cell fitness, as measured by decreased proliferation and clonogenic potential. Clinically relevant CDK9 inhibitors show variable efficacy in vivo, but the CNS-penetrant zotiraciclib achieved a significant prolongation in xenograft survival. CONCLUSION: CDK9 catalytic activity represents a druggable vulnerability underpinning Myc-driven transcriptional programs. The development of CNS-penetrant CDK9 inhibitors may open new avenues for rational therapy in these high-risk medulloblastomas.
Anemia due to hypogonadism can be successfully treated in hypogonadal men with testosterone replacement: Real-World data from a controlled Registry Study
Authors: A. Yassin, K.S. Haider, R.A. Talib, O.M. Aboumarzouk, R.M. Al-Zoubi, A.R. Al-Qudimat, M.A. Rejeb, A.A. Al Ansari
Journal: European Urology (2022)
Correspondence to " Emollients in infancy to prevent atopic dermatitis: A systematic review and meta‐analysis"
Authors: Maeve M. Kelleher, Suzie Cro, Rachel Phillips, Hywel C. Williams, Adrian J. Lowe, Robert J. Boyle
Journal: Allergy (2022)

MK, SC, RP and HCW report no conflict of interest. AJL reports: My institution has received National Health and Medical Research Council grant and fellowship funding to undertake a skin barrier intervention study. I also declare that Primus Pharmaceuticals and PuraCap Pharmaceuticals have donated EpiCream (a skin barrier treatment) for use in these studies, free of charge. I have also received an investigator-initiated grant from GSK for unrelated research. RJB reports: I have received personal payment for participating in advisory boards for DBV Technologies and Prota Therapeutics, which develop allergy diagnostics or treatments; have received payment for designing a clinical trial for Dairy Goat Co-operative; and have received personal payment for providing expert testimony in a class action related to an infant formula health claim concerning the development of allergic conditions.
Ultrastructural, endocrinological and reproductive effects of experimental unilateral cryptorchidism on the contralateral exocrine testicular function in the rabbit model
Authors: F. Dimitriadis, C. Tsiampali, A. Zachariou, C. Mamoulakis, E.N. Symeonidis, A. Karagiannis, A. Kaltsas, P. Tsounapi, A. Takenaka, N. Sofikitis
Journal: European Urology (2022)
Factors associated with the occurrence of myocardial infarction in patients treated for melanoma.
Authors: Xianying Pan, Devashish Verma, Jiayin Zhang, Yifan Zhang, Xiaomei Ma
Journal: Journal of Clinical Oncology (2022)

10562 Background: Treatments for melanoma increasingly involve the use of immune checkpoint inhibitors (ICIs), which are associated with cardiac toxicities. Our study aims to examine predictors of myocardial infarction (MI) in melanoma patients receiving treatment. Methods: The United Healthcare (Optum Clinformatics) Closed Claims + Lab Results Database (01/2007 – 03/2021) was used to examine factors potentially associated with the occurrence of hospitalized MI in melanoma patients. Adult patients were included if they: 1) had ≥12 months of continuous insurance coverage at baseline; 2) had ≥2 outpatient or ≥1 inpatient claims with an International Classification of Diseases (ICD) code indicative of melanoma; 3) received ≥1 type of cancer treatment (surgery, chemotherapy, radiotherapy, ICI, or targeted therapy); 4) had a claim with a melanoma ICD code within 5 days before the first cancer treatment; and 5) had no history of MI at baseline. Baseline was defined as the year prior to the first date of treatment; MI occurrence was identified from inpatient claims. We conducted a time-to-event (MI) analysis using a multivariate Cox proportional hazards regression model, with backward selection and death as a competing risk. Results: A total of 42,101 patients (58.8% male; median age of 68 yrs at baseline) were included in the study. Of these, 954 patients (2.3%) experienced a MI, and 5,578 (13.2%) died before having a MI. Compared with patients who underwent surgery only, those who received multiple treatments with an ICI were more likely to have a MI (hazard ratio [HR] = 1.25, 95% confidence interval [CI]: 1.01-1.55; Table). Men had a higher risk than women (HR = 1.47, 95% CI: 1.27-1.71), as did older people (compared with 65-74-yr-olds, HRs were 0.24, 0.49, 1.41, and 2.06 for &lt;55-, 55-64-, 75-84-, and ≥85-yr-olds, respectively; all P&lt;.05). Being Asian and having certain comorbidities at baseline were also associated with a higher MI risk (Table). Conclusions: In this retrospective cohort analysis of patients with melanoma, we observed an increased risk of MI among patients who received multiple treatments with ICIs, compared with surgery only. More research is needed to further elucidate predictors of MI events related to cancer treatment. [Table: see text]